Activity
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| Retinal disorders v8.28 | CYP2U1 | Arina Puzriakova Tag Q3_25_promote_green tag was added to gene: CYP2U1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.28 | CYP2U1 | Arina Puzriakova Phenotypes for gene: CYP2U1 were changed from to Spastic paraplegia 56, autosomal recessive, OMIM:615030; retinal disorder, MONDO:0005283 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.27 | CYP2U1 | Arina Puzriakova Publications for gene: CYP2U1 were set to 26914923; 34828401; 39605873 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.26 | CYP2U1 | Arina Puzriakova Classified gene: CYP2U1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.26 | CYP2U1 | Arina Puzriakova Gene: cyp2u1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.25 | CYP2U1 | Ida Ertmanska commented on gene: CYP2U1: Comment on list classification: As reviewed by Cassandra Smith, individuals with biallelic variants in CYP2U1 may present with retinal abnormalities, which fits into the scope of this panel - there at least 8 unrelated individuals reported in literature. The retinal disease has a variable age of onset (ranging from 6 to 32 years old in reported cases), sometimes appearing as the first symptom, before spasticity. Based on the available evidence, CYP2U1 should be rated Green for Retinal disorders. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.25 | CYP2U1 | Ida Ertmanska edited their review of gene: CYP2U1: Changed publications to: 23176821, 26914923, 29034544, 33107650, 34546337, 34828401, 38058766, 39605873 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.25 | CYP2U1 | Ida Ertmanska edited their review of gene: CYP2U1: Changed publications to: 23176821, 26914923, 33107650, 34828401, 38058766, 39605873 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.25 | CYP2U1 | Ida Ertmanska Deleted their comment | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.25 | CYP2U1 |
Ida Ertmanska commented on gene: CYP2U1: CYP2U1 is known to cause hereditary spastic paraplegia, with a variable spectrum of other symptoms being reported: intellectual disability, dystonia, pseudoxanthoma elasticum, and visual impairments (pigmentary degenerative maculopathy, loss of visual acuity, photophobia). There are at least 8 unrelated individuals with retinal abnormalities with biallelic variants in CYP2U1, harbouring missense, stop-gained, splice-altering, and frameshift variants (PMID: 23176821, 26914923, 33107650, 34828401, 38058766, 39605873). The retinal disease has a variable age of onset (ranging from 6 to 32 years old in reported cases) – sometimes appearing as the first symptom, before spasticity (e.g. PMID:26914923, 39605873). FUNCTIONAL EVIDENCE: A Cyp2u1−/− mouse model recapitulated the retinal impairments observed in patients – mice exhibited a late-onset (18 mo) ophthalmologic phenotype characterized by a cone dystrophy (PMID: 34546337 Pujol et al., 2021). Skin fibroblasts of an individual with c.61_73del, p.(Leu21Trpfs∗19) in CYP2U1 showed reduced oxygen consumption compared to controls, as well as structural abnormalities of the mitochondrial membrane (PMID: 23176821 Tesson et al., 2012). Expressing CYP2U1 with missense variants in HEK293T cells demonstrated that most missense variants were functionally inactive, due to loss of proper heme binding or destabilization of the protein structure (PMID: 29034544 Durand et al., 2018). Thus, the proposed disease mechanism is LoF leading to mitochondrial dysfunction - a common driver for degenerative retinal disease. Based on the available evidence, CYP2U1 should be rated Green for Retinal disorders. The gene is associated with Spastic paraplegia 56, autosomal recessive (OMIM:615030, accessed 17th Sep 2025). It is also Definitive for CYP2U1-related spastic paraplegia in G2P (G2P00349). |
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| Retinal disorders v8.25 | CYP2U1 | Ida Ertmanska reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23176821, 26914923, 33107650, 34828401, 38058766, 39605873; Phenotypes: Spastic paraplegia 56, autosomal recessive, OMIM:615030, retinal disorder, MONDO:0005283; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.14 | CYP2U1 | Arina Puzriakova Publications for gene: CYP2U1 were set to PMID: 26914923; 34828401; 39605873 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v8.4 | CYP2U1 |
Cassandra Smith gene: CYP2U1 was added gene: CYP2U1 was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYP2U1 were set to PMID: 26914923; 34828401; 39605873 Review for gene: CYP2U1 was set to GREEN Added comment: In some families, it appears visual symptoms may present before spasticity/neurological phenotype. PMID: 26914923 - Three patients from one family, where visual issues (pigmentary degenerative maculopathy) presented before spasticity. Biallelic loss of function variant identified PMID: 34828401 - Patient presenting with bilateral progressive visual loss and photophobia. Biallelic loss of function variant identified PMID: 39605873 - Two sibs with compound heterozygous variants. One had manifest neurological abnormalities since early childhood; the second had no neurological abnormalities. Both had opthalmological abnormalities Sources: Literature |
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